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Endocrinology > Lec6 Adrenal cortex: Hormones & Physiology > Flashcards

Lec6 Adrenal cortex: Hormones & Physiology Flashcards

Anatomy of adrenal cortex Synthesis and actions of glucocorticoids Synthesis and actions of mineralocorticoids Therapeutic uses of corticosteroids

1
Q

What percentage of the adrenal gland is cortex?

A

90%

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2
Q

What percentage of the adrenal gland is the inner medulla?

A

10%

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3
Q

What is the function of the medulla?

A

Neuroendocrine tissue which secretes catecholamines and is responsible for the stress response

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4
Q

What is the function of the adrenal cortex?

A

Involved in salt, glucose and stress homeostasis

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5
Q

Which out of the two: functioning adrenal medulla or functioning adrenal cortex is essential for life?

A

Adrenal cortex

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6
Q

What type of hormones does the adrenal cortex synthesise?

A

Steroid hormones - all with similar chemical structure

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7
Q

What molecule are the steroid hormones derived from and where does this molecule come from?

A

Steroid hormones are synthesised from cholesterol

Cholesterol comes from the diet or is synthesised within the gland itself

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8
Q

What are the three layers of the adrenal cortex and what do they synthesise?

A

Outer zona glomerulosa
Middle zona fasciculata
Inner zona reticularis

They synthesise adrenocortical steroid hormones

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9
Q

How do the cells within these three layers produce different steroid hormones?

A

because they possess different enzymes which produce different steroid hormones with a variety of effects

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10
Q

How are steroid hormones classified?

A

according to their predominant action

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11
Q

What are the major secretions of the adrenal cortex?

A

Glucocorticoids e.g. cortisol

Mineralocorticoids e.g. aldosterone

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12
Q

What is the function of glucocorticoids?

A

To control blood glucose

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13
Q

What is the function of mineralocorticoids?

A

To control sodium and potassium concentrations

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14
Q

What is the Synthetic pathway?

A

The synthetic pathway is all the steps which leads from cholesterol to becoming aldosterone, cortisol and testosterone

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15
Q

Which enzyme does the zona glomerulosa have?

A

18-hydroxylase enzyme - leading to aldosterone synthesis

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16
Q

Which enzyme does the zona fasciculata and zona reticularis have?

A

17alpha hydroxylase
Therefore 17alpha-hydroxypregnenolone and 17alpha-hydroxyprogesteron and the hormones derived from them are synthesised

i.e. cortisol and androgens (testosterone)

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17
Q

Where is cortisol synthesised?

A

Zona fasciculata

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18
Q

Where are androgens synthesised?

A

Zona reticularis

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19
Q

Under normal circumstances, what does the adrenal cortex secrete in small quantities?

A

Androgens i.e. dehydroepiandrosterone, androstenedione and testosterone and female oestrogens e.g. oestrodiol

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20
Q

When does the secretion of testosterone from the adrenal cortices increase?

A

Only in adrenal disorders, when things go wrong otherwise testosterone is secreted in very small amounts

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21
Q

Describe the control of cortisol secretion

A

The hypothalamus secreted corticotrophin releasing hormone (CRH) which acts on the pituitary gland to secrete adrenocorticotrophic hormone (ACTH). ACTH acts on the adrenal cortex to secrete cortisol

Cortisol has a negative feedback loop preventing further release of CRH from the hypothalamus

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22
Q

Describe the secretion pattern of ACTH

A

ACTH secretion is pulsatile
Peak ACTH very early in the morning
Nadir in the middle of the night

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23
Q

When does increased secretion of ACTH occur?

A

During prolonged periods of stress

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24
Q

Describe the secretion pattern of cortisol

A

Secretion of cortisol is also pulsatile

But the peak and nadir are about 2 hours after those of ACTH

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25
Q

What does the pattern of ACTH and cortisol secretion relate to and when is this disturbed?

A

Sleep-wake cycles
Disturbed by shift work and long haul travel
Jet lag caused by a perturbation to the diurnal rhythm of ACTH and cortisol

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26
Q

What percentage of cortisol is free/ unbound?

A

10%

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27
Q

What are the proteins that cortisol is bound to and in what percentages?

A

Corticosteroid binding globulin or transcortin (75%)

Albumin (15%)

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28
Q

Pregnancy is associated with an increase in which cortisol binding protein?

A

CBG

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29
Q

What does an increase in CBG during pregnancy correspond to?

A

An increase in the amount of cortisol in the blood to maintain the free amount

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30
Q

How are glucocorticoids metabolised?

A

Steroid hormones are not water soluble

They are metabolised by the liver - glucuronidated to form water soluble forms that can be excreted in the urine

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31
Q

What other hormones are also bound to CBG and albumin?

A

Other glucocorticoids and progesterone

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32
Q

How are progesterone and cortisol metabolised?

A

Hepatic metabolism allows them to be rapidly excreted

33
Q

How do glucocorticoids produce their effects?

A

By acting on intracellular glucocorticoid receptors and alterations in gene expression
This results in a delay in the order of hours/days

34
Q

When are the effects of cortisol rapid?

A

In the feedback inhibition of ACTH secretion

35
Q

At physiological concentrations, the most important actions of cortisol are on what?

A

Carbohydrate metabolism

36
Q

How does the effects of cortisol oppose those of insulin?

A

Antagonise the effect of insulin on cellular uptake of glucose
Stimulates glycogenolysis
Stimulates hepatic gluconeogenesis

37
Q

What are the effects of cortisol on growth hormone and catecholamines?

A

Cortisol potentiates the effects of growth hormone and catecholamines therefore stimulating lipolysis and mobilisation of fatty acids

38
Q

What does cortisol cause in excessive concentrations?

A

Fat deposition in the face, trunk and intrascapular region of the shoulder

39
Q

What are the effects of cortisol on the liver?

A

Cortisol stimulates amino acid uptake and therefore enhanced gluconeogenesis

40
Q

What are the effects of cortisol in the periphery?

A

Inhibits amino acid uptake and protein synthesis leading to net loss of skeletal muscle and impeding growth

41
Q

Glucocorticoids are able to stimulate aldosterone receptors. True or false

A

True

42
Q

Name the enzyme possessed by aldosterone sensitive tissues that converts cortisol into inactive cortisone

A

11 beta hydroxysteroid dehydrogenase

43
Q

When are there mineralocorticoids actions of glucocorticoids?

A

At very high concentrations of glucocorticoids

44
Q

What is another effect of excess cortisol?

A

Enhanced vasoconstrictor responses to catecholamines resulting in raised blood pressure

45
Q

What psychological effects can be produced by glucocorticoids?

A

Feelings of elation or sedation

46
Q

At what times is there a rapid secretion of ACTH and cortisol?

A

at times of psychological and physiological stress e.g. trauma, infection or hypoglycaemia

47
Q

What is the effect of glucocorticoids on the immune system?

A
  1. Inhibition of phospholipase A2
  2. Reduced synthesis of inflammatory mediators
  3. Suppression of the immune system
  4. Stop antibody production
48
Q

What is the most important response of glucocorticoids

A

Response to stress

49
Q

What happens in the absence of corticosteroids?

A

Death within 48 hours

50
Q

What happens in a reduction in corticosteroids?

A

Inability to deal with certain stressful conditions e.g. cold mornings

51
Q

Why might it appear that steroids are acting contrary to the individual’s best interests?

A

because they mask the damage

Suppress the inflammatory and immune responses that allow wound healing and tissue repair to occur

52
Q

What do steroids allow you to do?

A

removes pain, lack of awareness of severity of the situation i.e. function despite the presence of illness and or injury

53
Q

What happens to the concentration of the corticosteroids once the individual is in a safe place?

A

The concentrations of corticosteroids go down

54
Q

What are the two physiologically most important mineralocorticoids?

A

Aldosterone and 11-deoxycorticosterone

55
Q

Which are more important? Glucocorticoids or mineralocorticoids?

A

Glucocorticoids

56
Q

What role does ACTH play in secretion of aldosterone?

A

Secretion of aldosterone is relatively uninfluenced by ACTH secretion
ACTH secretion causes the initial conversion of cholesterol to pregenenolone

57
Q

What is the major factor in the control of aldosterone secretion?

A

Renin-angiotensin-aldosterone system

e.g. when blood pressure drops - renin is secreted

58
Q

What else stimulates secretion of aldosterone?

A

Trauma, anxiety, hyperkalaemia and hyponatraemia

59
Q

What inhibits aldosterone secretions?

A

Atrial natriuretic peptide (ANP)

60
Q

What percentage of aldosterone is protein bound within the circulation?

A

50%

61
Q

How does aldosterone have its effects?

A

Aldosterone acts on intracellular receptors which cause expression of ion channels to allow sodium and potassium ions across the membrane

62
Q

What are the effects of aldosterone?

A

Sodium reabsorption in the distal tubule of the kidney in exchange for potassium ions or hydrogen ions

63
Q

Where does aldosterone have its lesser effects?

A

In the ascending loop of Henley, proximal tubule and collecting duct as well as the colon, sweat and salivary glands

64
Q

How does controlling sodium reabsorption influence water reabsorption?

A

Aldosterone causes sodium ion reabsorption –> increased sodium ion concentration –> causing water reabsorption in the collecting duct via ADH secretion

65
Q

What effect does the interaction of the renin-angiotensin system, aldosterone and ADH have on the body?

A

Controls blood volume and therefore influences blood pressure

66
Q

What are the pharmacological uses of glucocorticoids?

A

Replacement therapy
Immunosuppressive or anti-inflammatory effects in conditions e.g. arthritis, asthma/allergies/ treatment of proliferative conditions e.g. leukaemia

67
Q

What are the pharmacological uses of mineralocorticoids?

A

Only for replacement therapy

68
Q

What is used instead of aldosterone for replacement therapy and why?

A

Fludrocortisol because the short plasma half- life of aldosterone renders it unsuitable

69
Q

Are glucocorticoids orally active?

A

Most glucocorticoids are orally active

70
Q

Are glucocorticoids absorbed through the skin

A

This varies as does plasma half-life

71
Q

What are the adverse effects associated with use of glucocorticoids

A 
Suppression of wound healing 
Exacerbation of infections 
Inhibition of growth in children
Osteoporosis in adults 
Development of diabetes mellitus 
Development of Cushing's syndrome
72
Q

What does chronic administration of exogenous glucocorticoids result in?

A

Suppression of ACTH secretion leading to atrophy of the adrenal cortex

73
Q

If steroid therapy is stopped suddenly, what can happen?

A

The adrenal cortex is unable to secrete endogenous corticosteroids and the patient suffers an Addisonian crisis

74
Q

What is an Addisonian crisis?

A

Hyperactivity of adrenal gland - not able to produce the hormones needed & unable to respond to stress –> fatal

75
Q

What is the disadvantage of anti-inflammatory corticosteroids?

A

They hide the symptoms but do not treat the underlying problem which may worsen

76
Q

What is hydrocortisone? How does it act

A

A natural glucocorticoid secreted from the adrenal cortex.

It acts via intracellular glucocorticoid receptors to influence gene expression

77
Q

What is hydrocortisone used for?

A

Hormone replacement therapy
Anti-inflammatory agent
Immunosuppressant

78
Q

What are the adverse effects of hydrocortisone?

A

Hyperglycaemia
Osteoporosis
Cushing’s syndrome

Endocrinology (11 decks)

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